Cell transplantation is a proven method of treatment for certain immunological disorders and has shown promising effects for a variety of medical conditions including Parkinson's, Huntington's, stroke, spinal cord injury, myocardial infarction, and bone repair. Although a variety of transplanted progenitor cells and stem cells have had some degree of success in improving functional recovery, cell survival after transplantation is often poor and unpredictable, and has been directly correlated with functional outcome of the treatment in animal models. Therefore, there is a strong need to develop more reliable and efficient cell transplantation procedures.
Hydrogels are ideal materials for implantation because they introduce very low levels of foreign matter into the body and promote maximum diffusion of biomolecules throughout the scaffold due to their high water content. Hydrogel crosslinks can be either chemical, or physical. Since many chemical crosslinkers are toxic and result in non-injectable gels, physical hydrogels are preferred for many biomedical applications. Due to their unique structure, many physical hydrogels are shear-thinning, allowing them to be injected easily, an important criterion for non-invasive cell and drug delivery.
However, the assembly of polymers into physical hydrogels for cell encapsulation has mostly been governed by the use of external triggers. In these systems, cells are mixed with precursor macromolecules in the solution phase under specific environmental conditions. Following this, cells are encapsulated by exposure to a sudden change in pH, temperature, or ionic concentration to induce a solution to gel phase transition either in vitro or in situ. For example, common triggers for cell encapsulation by physical hydrogels include temperature sweeps from 4° C. to 37° C. for collagen and Matrigel; pH shifts from 2.0-2.5 to 7.4 for PuraMatrix and leucine-zipper systems; and cation concentration increases ranging from 20 to 200 mM for alginate and self-assembled peptide amphiphiles. These materials are generally designed to be in the gel phase at physiological conditions, requiring that cells be momentarily exposed to non-ideal environmental conditions in the sol phase (often a combination of low pH and temperature). Upon injection, the material equilibrates to physiological conditions and undergoes a phase change to the gel state. Because transplanted cells are highly sensitive to these non-physiological conditions, these triggers can be irreversibly detrimental to the encapsulated cells and accompanying proteins; and furthermore, these environmental conditions can be difficult to reproducibly control in a clinical setting. Therefore, current injection techniques within physical hydrogels can result in substantial loss of transplanted viable cells. This is of importance because cell viability and reproducibility in clinical settings have been directly correlated to the successful outcomes of these cell transplantation procedures. The present invention addresses at least some of the current problems and advances the art by introducing a physical hydrogel capable of encapsulating cells, drugs and proteins without subjecting them to variations in pH, temperature, or ionic strength.